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Extreme Atherosclerotic Cardiovascular Disease (ASCVD) Risk Recognition

  • Macrovascular Complications in Diabetes (VR Aroda and A Getaneh, Section Editors)
  • Published:
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A Correction to this article was published on 06 November 2019

This article has been updated

Abstract

Purpose of Review

To distinguish extreme and very high atherosclerotic cardiovascular disease (ASCVD) event risk based on prospective epidemiological studies and clinical trial results.

Recent Findings

Clinical practice guidelines have categorized patients with either a history of one or more “clinical ASCVD” events or “coronary heart disease (CHD) risk equivalency” to be at “very high risk” for a recurrence or a first event, respectively. A 20% or greater 10-year ASCVD risk for a composite 3-point “major” atherosclerotic cardiovascular event (MACE) of non-fatal myocardial infarction (MI), non-fatal stroke, or cardiovascular death can serve as an arbitrary definition of those at “very high risk.” Exclusion of stroke may underestimate risk of “hard” endpoint 10-year ASCVD risk and addition of other potential endpoints, e.g., hospital admission for unstable angina or revascularization, a 5-point composite MACE, may overinflate the risk definitions and categorization. “Extreme” risk, a descriptor for even higher morbidity and mortality potential, defines a 30% or greater 10-year 3-point MACE (ASCVD) risk. In prospective, epidemiological studies and randomized clinical trial (RCT) participants with an initial acute coronary syndrome (ACS) within several months of entry into the study meet the inclusion criteria assignment for extreme risk. In survivors beyond the first year of an ASCVD event, “extreme” risk persists when one or more comorbidities are present, including diabetes, heart failure (HF), stage 3 or higher chronic kidney disease (CKD), familial hypercholesterolemia (FH), and poorly controlled major risk factors such as hypertension and persistent tobaccoism. “Extreme” risk particularly applies to those with progressive or multiple clinical ASCVD events in the same artery, same arterial bed, or polyvascular sites, including unstable angina and transient ischemic events. Identifying asymptomatic individuals with extensive subclinical ASCVD at “extreme” risk is a challenge, as risk engine assessment may not be adequate; individuals with genetic FH or those with diabetes and Agatston coronary artery calcification (CAC) scores greater than 1000 exemplify such threatening settings and opportunities for aggressive primary prevention.

Summary

Heterogeneity exists among individuals at risk for clinical ASCVD events; identifying those at “extreme” risk, a more ominous ASCVD category, associated with greater morbidity and mortality, should prompt the most effective global cardiometabolic risk reduction.

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Change history

  • 06 November 2019

    The original version of this article unfortunately contained a mistake.

Abbreviations

AACE:

American Association of Clinical Endocrinologists

ACE:

American College of Endocrinology

ACC:

American College Cardiology

AHA:

American Heart Association

ASCVD:

Atherosclerotic cardiovascular disease

ACS:

Acute coronary syndrome

ATP:

Adult treatment panel

BP:

Blood pressure

CAC:

Coronary artery calcification

CAD:

Coronary artery disease

CCTA:

Coronary computed tomography angiography

CHD:

Coronary heart disease

CHF:

Congestive heart failure

CI 95%:

Confidence interval

CKD:

Chronic kidney disease

CVD:

Cardiovascular disease

DM:

Diabetes mellitus

eGFR:

Estimated glomerular filtration rates

ESC:

European Societies of Cardiology

EAS:

European Atherosclerosis Society

FH:

Familial Hypercholesterolemia

HeFH:

Heterozygous familial hypercholesterolemia

HoFH:

Homozygous familial hypercholesterolemia

HF:

Heart failure

HR:

Hazard ratio

HTN:

Hypertension

HDL-C:

High-density lipoprotein cholesterol

LDL-C:

Low-density lipoprotein cholesterol

LVH:

Left ventricular hypertrophy

MI:

Myocardial infarction

MACE:

Major adverse cardiovascular events

NCEP:

National Cholesterol Education Program

NHLBI:

National Heart, Lung, and Blood Institute

NLA:

National Lipid Association

NF-MI:

Non-fatal myocardial infarction

NNT:

Number needed to treat

PAD:

Peripheral artery disease

PCSK9:

Proprotein convertase subtilisin/kexin type 9

PEP:

Primary endpoint

RCTs:

Randomized clinical trials

RR:

Relative risk

T1DM:

Type 1 diabetes mellitus

T2DM:

Type 2 diabetes mellitus

TIA:

Transient ischemic attack

TG:

Triglycerides

UA:

Unstable angina

4-D:

Die Deutsche Diabetes Dialyse

AURORA:

A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events

CORONA:

Controlled Rosuvastatin Multinational Trial in Heart Failure

FOURIER:

Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk

FHS:

Framingham Heart Study

FOS:

Framingham Offspring Study

GISSI-HF:

Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI)-Heart Failure Study

GRACE:

Global Registry of Acute Coronary Events

IMPROVE-IT:

Improved Reduction of Outcomes: Vytorin Efficacy International Trial

MRFIT:

Multiple Risk Factor Intervention Trial

OASIS:

Organization to Assess Strategies for Ischemic Syndromes registry

ODYSSEY:

Outcomes Trial to determine whether the addition of the PCSK9 antibody alirocumab to intensive statin therapy reduces cardiovascular morbidity and mortality after ACS

PROVE-IT:

Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction 22) trial

REACH:

Reduction of Atherothrombosis for Continued Health registry

REVERSAL:

Reversal of Atherosclerosis with Aggressive Lipid Lowering trial

RUTHERFORD-2:

Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study-2

SHARP:

Study of Heart and Renal Protection

SHS:

Strong Heart Study

TNT:

Treating to New Targets

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Acknowledgments

The author would like to thank Dr. Asqual Getaneh for critical review, feedback, and edits of earlier and current drafts of this review.

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  1. Department Medicine, Division Endocrinology, Diabetes, Metabolism, University California, Irvine (UCI), School of Medicine, Irvine, CA, 92697, USA

    Paul D. Rosenblit

  2. Diabetes Out-Patient Clinic, UCI Medical Center, Orange, CA, 92868, USA

    Paul D. Rosenblit

  3. Diabetes/Lipid Management & Research Center, 18821 Delaware St., Suite 202, Huntington Beach, CA, 92648, USA

    Paul D. Rosenblit

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12-month 1/1/18-12/31/18 disclosure

Paul D. Rosenblit received clinical trial research site funding from Amgen, AstraZeneca, Dexcom, GlaxoSmithKline, Ionis, Mylan, and Novo Nordisk. He received speaker faculty honoraria from Akcea, Amgen, Merck, and Novo Nordisk. He received advisory board honoraria from Akcea, Esperion, and Novo Nordisk.

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Rosenblit, P.D. Extreme Atherosclerotic Cardiovascular Disease (ASCVD) Risk Recognition. Curr Diab Rep 19, 61 (2019). https://doi.org/10.1007/s11892-019-1178-6

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